Abstracts

RATIONALE: Convulsions induced by pentylenetetrazol (PTZ) in immature rats provoke an long-term enhancement of cholinergic (ACh) transmission in area CA3 of hippocampus, as manifested by the fact that, in slices, the AChE inhibitor eserine (10 ?M) will then induce spontaneous synchronous epileptiform activity, an effect never observed in controls (Meilleur et al., Neuroreport 11:521-524, 2000). METHODS: We have investigated the temporal profile of this enhancement, and compared it in animals having sustained generalized convulsions when immature (P20) or adult (P60). Field potentials recordings were obtained from CA3 of hippocampal slices after a short (10 days) or long (>40 days) interval post-injection (ipi). RESULTS: In rats PTZ-injected when immature, the enhancement by eserine was observed in 6/15 of short ipi rats and 8/8 of long ipi rats, suggesting a progressive and permanent effect. An inverse temporal profile was observed in rats PTZ-injected as adults: 7/7 rats showed the enhanced response to eserine after a short ipi, but only 3/11 after a long ipi, indicating that PTZ-induced convulsions in adults entailed only transient changes in cholinergic transmission. To test whether the long-term enhancement of cholinergic transmission by early convulsions could be due to a proliferation of the cholinergic innervation, we used a quantitative ChAT-immunocytochemical method to compare the extent of the hippocampal cholinergic axon network in two pairs of adult rats, PTZ- or saline-injected at P20. No significant differences were found in either the distribution or the length of ACh axons between control and PTZ-injected rats. CONCLUSIONS: The enhancement of cholinergic transmission in hippocampal region CA3 is a long term effect of early, but not adult, seizures. This effect is not associated with modifications of the cholinergic neuronal network. Other mechanisms are currently being investigated. (Supported by NSERC, The Ste-Justine Hospital Foundation and MRC Grant MT-3544).